Citations

SummaryThe rituximab extended schedule or retreatment trial (RESORT; E4402) was a phase 3 randomized prospective trial comparing maintenance rituximab (MR) versus a retreatment (RR) dosing strategy in asymptomatic, low tumour burden indolent lymphoma. A planned exploratory sub‐study compared the two strategies for small lymphocytic (SLL) and marginal zone lymphomas (MZL). Patients responding to rituximab weekly × 4 were randomized to MR (single dose rituximab every 3 months until treatment failure) or RR (rituximab weekly × 4) at the time of each progression until treatment failure. The primary endpoint was time to treatment failure (TTTF). Patients with SLL (n = 57), MZL (n = 71) and unclassifiable small B‐cell lymphoma (n = 3) received induction rituximab. The overall response rate (ORR) was 40% [95% confidence interval (CI) 31–49%; SLL ORR 22·8%; MZL ORR 52·1%]; all 52 responders were randomized. At a median of 4·3 years from randomization, treatment failure occurred in 18/23 RR and 15/29 MR. The median TTTF was 1·4 years for RR and 4·8 years for MR (P = 0·012); median time to first cytotoxic therapy was 6·3 years for RR and not reached for MR (P = 0·0002). Survival did not differ (P = 0·72). In low tumour burden SLL and MZL patients responding to rituximab induction, MR significantly improved TTTF as compared with RR.

Abstract Purpose: Preclinical studies suggest that SNPs in the Fc gamma receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain. Experimental Design: We prospectively obtained specimens for genotyping in the rituximab extended schedule or re-treatment trial (RESORT) study, in which 408 previously untreated, low tumor burden follicular lymphoma (FL) patients were treated with single agent rituximab. Patients received rituximab in 4 weekly doses and responders were randomized to rituximab re-treatment (RR) upon progression versus maintenance rituximab (MR). SNP genotyping was performed in 321 consenting patients. Results: Response rates to initial therapy and response duration were correlated with the FCGR3A SNP at position 158 (rs396991) and the FCGR2A SNP at position 131 (rs1801274). The response rate to initial rituximab was 71%. No FCGR genotypes or grouping of genotypes were predictive of initial response. A total of 289 patients were randomized to RR (n = 143) or to MR (n = 146). With a median follow-up of 5.5 years, the 3-year response duration in the RR arm and the MR arm was 50% and 78%, respectively. Genotyping was available in 235 of 289 randomized patients. In patients receiving RR (n = 115) or MR (n = 120), response duration was not associated with any FCGR genotypes or genotype combinations. Conclusions: Based on this analysis of treatment-naïve, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab. Clin Cancer Res; 22(4); 821–6. ©2015 AACR. See related commentary by Cartron et al., p. 787

We recently defined event‐free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age‐ and sex‐matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline‐based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c‐statistic = 0.671) in the validation dataset compared to the IPI (c‐statistic = 0.649) or the NCCN‐IPI (c‐statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps. Am. J. Hematol. 91:179–184, 2016. © 2015 Wiley Periodicals, Inc.

Hidradenocarcinoma is a rare aggressive form of cutaneous adnexal skin carcinoma originating from the sweat gland. Due to its low incidence, prognostic and treatment strategies are still being explored both for primary and advanced disease. This tumor most often presents as either solid or cystic appearing subcutaneous nodules, which may be associated with pruritus or ulceration. To date the mainstay of treatment for local disease has been surgical excision; however, the paucity of historical data available has shown that these tumors often behave aggressively with high rates of local recurrence, metastasis, and poor overall outcomes. There are few case reports describing the utility of radiation therapy in the treatment of hidradenocarcinoma. Herein, we present a case of metastatic apocrine hidradenocarcinoma in a 32-year-old Caucasian male. The patient initially underwent excisional biopsy which confirmed the diagnosis of poorly differentiated, highly infiltrative, apocrine hidradenocarcinoma. He received systemic chemotherapy for metastatic disease, followed by radiation therapy to areas of grossly palpable adenopathy. Prior to radiation therapy the patient had an enlarged hypermetabolic conglomerate of lymph nodes in the right axilla, and borderline enlarged low activity nodes within the left axilla. He received 3 cycles of chemotherapy followed by tamoxifen and radiation therapy (50.4 Gy in 28 fractions) to areas of progressive disease in the bilateral axilla, lower neck, and axillary skin. Following treatment, the patient had complete resolution of skin nodules and improvement of his pruritus. While the role of radiation therapy in the treatment of hidradenocarcinoma has not been well established, this case report demonstrated the potential benefit of external beam radiotherapy in the management of this rare disease.

SummaryThe International Prognostic Score (IPS‐7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS‐7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS‐7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS‐7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS‐3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P = 0·0001) and OS (P < 0·0001)]. IPS‐3 outperformed the IPS‐7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS‐7 low risk patients were re‐classified as intermediate risk and 13% of IPS‐7 intermediate risk patients as low risk. For patients with advanced HL, the IPS‐3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.

SummaryPatients with early stage diffuse large B‐cell lymphoma (DLBCL) receive RCHOP (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with involved field radiotherapy (IFRT). Anti‐CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional complete response (CR) rate of ≥75% to RCHOP and 90Yttrium‐ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4–6 cycles of RCHOP followed by RIT [14·8 MBq/kg (0·4 mCi/kg)]; patients with positron emission tomographypositive sites of disease after RCHOP/RIT received 30 Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed CR. Forty‐eight patients proceeded to RIT. One partial responder after RIT received IFRT and achieved a CR. The best response after RCHOP + RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77–96%). With a median follow‐up of 5·9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty‐nine percent of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial.

Summary A persistently positive positron emission tomography ( PET ) scan during therapy for diffuse large B‐cell lymphoma ( DLBCL ) is predictive of treatment failure. A response‐adapted strategy consisting of an early treatment change to four cycles of R‐ ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R‐ CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET ‐positive patients received four cycles of R‐ ICE , PET ‐negative patients received two more cycles of R‐ CHOP . A ≥45% 2‐year progression‐free survival ( PFS ) for mid‐treatment PET ‐positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two‐year PFS was 70%; 42% [90% confidence interval (CI), 19–63%] for PET ‐positives and 76% (90% CI 65–84%) for PET ‐negatives. Three‐year overall survival ( OS ) was 69% (90% CI 43–85%) and 93% (90% CI 86–97%) for PET ‐positive and ‐negative cases, respectively. The 2‐year PFS for mid‐treatment PET ‐positive patients intensified to R‐ ICE was 42%, with a wide confidence interval due to the low proportion of positive mid‐treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials.